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J Biomol Screen. 2015 Jan;20(1):64-9. doi: 10.1177/1087057114551518. Epub 2014 Oct 2.

Development and validation of a high-throughput anti-Wolbachia whole-cell screen: a route to macrofilaricidal drugs against onchocerciasis and lymphatic filariasis.

Author information

1
Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, UK.
2
Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, UK Mark.Taylor@lstmed.ac.uk.

Abstract

There is an urgent need to develop new, safe, and affordable macrofilaricidal drugs for onchocerciasis and lymphatic filariasis treatment and control. The Anti-Wolbachia Consortium (A·WOL) aims to provide a novel treatment with macrofilaricidal activity by targeting the essential bacterial symbiont Wolbachia. The consortium is currently screening a diverse range of compounds to find new chemical space to drive this drug discovery initiative and address this unmet demand. To increase the throughput and capacity of the A·WOL cell-based screen, we have developed a 384-well format assay using a high-content imaging system (Operetta) in conjunction with optimized Wolbachia growth dynamics in the C6/36 Aedes albopictus mosquito cell line. This assay uses texture analysis of cells stained with SYTO 11 as a direct measure of bacterial load. This validated assay has dramatically increased the capacity and throughput of the A·WOL compound library screening program 25-fold, enriching the number of new anti-Wolbachia hits identified for further development as potential macrofilaricides for onchocerciasis and lymphatic filariasis.

KEYWORDS:

cell-based assays; fluorescence methods; high-content screening; phenotypic drug discovery

PMID:
25278497
DOI:
10.1177/1087057114551518
[Indexed for MEDLINE]

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